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Biomedical subjects

J Wernerman

Publications and source records attributed to J Wernerman.

At least 37 records · Page 2Linked to original sources
PubMed2002

Longitudinal pattern of glutamine/glutamate balance across the leg in long-stay intensive care unit patients.

BACKGROUND & AIMS: Progressive muscle wasting is a characteristic feature of patients treated at the intensive care unit (ICU). As a consequence, endogenous glutamine production by skeletal muscle may be compromised. We investigated the time pattern of the glutamine and glutamate net balance across the leg in long-stay ICU patients. METHODS: Critically ill patients with multiple organ failure that were expected to stay in the ICU for more than 3 days were included in a longitudinal study. Possible changes in amino acid net balance over the leg muscle were investigated overtime. The patients (n=20) were studied descriptively every third or fourth day, on a total of 2-7 occasions. MAIN RESULTS: The glutamine net release from leg muscles did not change significantly during the initial 2 weeks of ICU stay and was not related to the plasma concentration of glutamine. The net uptake of glutamate across the leg muscles was unaltered during this time period, but it was found to correlate statistically with both the arterial glutamate concentration and the glutamine net release. A continuous net release of phenylalanine indicated a progressive net loss of muscle protein in these patients. CONCLUSION: The net release of glutamine from skeletal muscle does not decrease in stabilized critically ill patients with multiple organ failure over the initial 2 weeks of ICU stay, despite progressive muscle wasting.

APACHE↗
PubMed2001

Growth hormone does not affect albumin synthesis in the critically ill.

OBJECTIVE: To study the effect of growth hormone (GH) on albumin synthesis in critically ill patients. DESIGN: Prospective randomized controlled study. SETTING: Two intensive care units, university hospital and county hospital, respectively. PATIENTS: Twenty-two critically ill patients in the intensive care unit. INTERVENTIONS: Albumin synthesis was measured twice in each patient, with a 5-day interval. The patients in the control group (n = 11) received standard intensive care unit (ICU) treatment between measurements, whereas those in the GH group (n = 11) also received 0.3 U/kg daily of human recombinant GH. MEASUREMENTS AND RESULTS: Albumin synthesis was measured by labeling with L-[2H5]phenylalanine. In the control group, the fractional synthesis rate (FSR) of albumin was 16.3+/-4.1%/day (mean and SD) in the first measurement and 15.7+/-4.2%/day 5 days later (NS), whereas in the GH group the corresponding values were 17.0+/-4.7%/day and 16.7+/-5.5%/day (NS). The calculated absolute synthesis rates of albumin, based on FSR and intravascular albumin mass, also showed no effect of GH. CONCLUSION: Albumin synthesis rates were consistently higher in the two groups of critically ill patients than previously reported values in healthy subjects. However, GH treatment for 5 days neither stimulated nor inhibited albumin synthesis rates in these critically ill patients.

APACHE↗
PubMed2001

Stress hormones initiate prolonged changes in the muscle amino acid pattern.

Eight healthy volunteers were given an infusion containing cortisol, glucagon and adrenaline during 6 h. Muscle biopsies were taken before and at 6, 12 and 24 h. During the infusion serum cortisol, glucagon, glucose and insulin were increased. The stress hormone infusion induced characteristic changes in the muscle and plasma amino acid patterns similar to those seen early in protein catabolism. Muscle glutamine decreased at 12 and 24 h by -18.2 +/- 3.8 and -28.8 +/- 4.8%, respectively. The branched chain amino acids decreased at 6 h by -54.6 +/- 4.2% while increased levels (by 54.7 +/- 13.1%) were seen at 24 h. Plasma amino acids decreased during the infusion period and returned to basal during the postinfusion period. Despite a short-term infusion during 6 h the muscle amino acid pattern was still affected at 12 and 24 h and some of the changes were more accentuated at those timepoints as compared with the changes seen at 6 h.

Adult↗
PubMed2001

A combined stress hormone infusion decreases in vivo protein synthesis in human T lymphocytes in healthy volunteers.

In vivo protein synthesis decreases in mononuclear cells following a combined stress hormone infusion given to healthy volunteers as a human trauma model. Here, the purpose was to further investigate this finding and to measure in vivo protein synthesis in isolated T lymphocytes. Furthermore, the effects of stress hormones on the lymphocyte subpopulations and mononuclear cells, characterized by flow cytometry and phytohemagglutinin (PHA)-induced and unstimulated proliferative responses in vitro, were elucidated. Healthy volunteers (n = 16) were randomized into 2 groups to receive either a stress hormone or a saline infusion for 6 hours. In vivo protein synthesis was studied before and after the treatment by measuring the incorporation of stable isotopically-labeled phenylalanine into lymphocyte and mononuclear cell proteins. Protein synthesis decreased after stress hormone infusion in both cell populations: in T lymphocytes from 13.0% +/- 0.7%/d (mean +/- SD) to 8.6% +/- 2.1%/d (P <.01) and in mononuclear cells from 13.3% +/- 1.2%/d to 6.3 +/- 2.0%/d (P <.001). No change in proliferative responsiveness in vitro was observed. The stress hormone infusion produced a decrease in the percentage of T helper CD3/CD4 from 41% to 18% (P <.001), T cytotoxic CD3/CD8 from 27% to 15% (P <.001), as well as total T CD3 cells from 69% to 35% (P <.001). There was an increase in the percentage of natural killer (NK) cells CD16/CD56 from 17% to 55% (P <.001). Determination of phenotypes expressed on activated T lymphocytes showed that CD3/HLA-DR was unchanged and CD3/CD25 decreased from 14% to 7% (P <.01) in the stress hormone group. The study showed that the decrease of in vivo protein synthesis was 34% in T lymphocytes as compared with 53% in mononuclear cells, when determined immediately after a 6-hour stress hormone infusion. This change was associated with a pronounced decrease in all lymphocyte subpopulations, except for the NK cells, which increased substantially.

Adult↗
PubMed2001

Stimulation of human albumin synthesis and gene expression by growth hormone treatment.

BACKGROUND AND AIMS: In this study the effects of acute (5 h) and short-term (5 days) GH treatment on albumin synthesis rates in man were investigated and related to changes in the availability of hepatic albumin mRNA. METHODS: 30 patients undergoing elective laparoscopic cholecystectomy were randomized into controls (n=10) or GH-treatment (12 U/dose) for 5 h or 5 days (n=10 in each group). Albumin mRNA levels (in liver biopsy specimens) were measured employing a quantitative polymerase chain reaction assay developed specifically for this purpose, whereas albumin synthesis was measured using [(2)H(5)]phenylalanine. RESULTS: The fractional synthesis rate of albumin was 6.0+/-0.9 %/day in the control group and 8.0+/-1.8 %/day and 8.3+/-1.7 %/day in the GH-treated groups, respectively (P<0.05 vs controls in both cases). The corresponding values for the concentration of albumin mRNA were 2.6+/-1.1 ng/microg total RNA, 2.9+/-0.8 ng/microg total RNA (NS) and 4.7+/-1.8 ng/microg total RNA in the "GH 5" group (P<0.01 vs controls). The changes in albumin synthesis were only partly explained by the differences in hepatic albumin mRNA levels (r=0.5, P<0.01). CONCLUSION: These results suggest that GH may induce a quick, gene expression-independent increase in albumin synthesis, which is sustained by a later-occurring increase in albumin gene expression.

Adult↗
PubMed2001

Growth hormone together with glutamine-containing total parenteral nutrition maintains muscle glutamine levels and results in a less negative nitrogen balance after surgical trauma.

BACKGROUND: Muscle protein catabolism, reflected by a decrease in glutamine (GLN), a decrease in muscle protein synthesis, and a negative nitrogen balance can be reduced by either administration of GLN or growth hormone (GH). In this study, the effects of a combination of GH and GLH were studied. METHODS: Patients (n = 16) undergoing abdominal operation were given total parenteral nutrition (TPN) containing either GLN alone or GLN together with GH (GH/GLN) during 3 postoperative days. The amino acid concentration and protein synthesis in muscle tissue and the nitrogen balance were measured. RESULTS: GH/GLN reduced nitrogen losses compared with GLN alone (-5.8 +/- 1.4 g nitrogen versus -10.6 +/- 1.1 g nitrogen, P <.05). GH/GLN maintained muscle GLN at preoperative levels compared with a 47.5% +/- 6.3% decline in the GLN group. A similar decrease was seen in the fractional synthesis rate of muscle protein postoperatively in both groups. CONCLUSIONS: GH has an additive effect given together with GLN on muscle amino acid metabolism, preventing the decrease in the GLN concentration in skeletal muscle and diminishing the loss of whole body nitrogen. However, the improvements in muscle amino acid concentrations and nitrogen loss were not associated with differences between the groups in muscle protein synthesis postoperatively.

Abdomen↗
PubMed2001

Total parenteral nutrition after surgery rapidly increases serum leptin levels.

OBJECTIVE: In humans, leptin is regulated by long-term changes in energy intake. However, short-term regulation of serum leptin by nutrients has been difficult to show. The aim of this study was to investigate whether short periods of fasting and stress sensitise the leptin response to nutrients. SUBJECTS AND EXPERIMENTAL PROTOCOL: Fourteen patients of normal weight undergoing elective open cholecystectomy were randomised into two groups. One group received saline infusion during surgery and for 24 h postoperatively. The other group also received saline during the surgical procedure, but total parenteral nutrition (TPN) was started immediately after surgery. Blood samples were drawn before as well as 2, 4, 8, 16, and 24 h after the start of surgery to determine the serum levels of leptin and other hormones. RESULTS: Postoperative TPN induced a significant rise in serum leptin within 6 h, reaching a more than fourfold increase within 14 h (P<0.001). Serum glucose and insulin levels increased within 2 h. Growth hormone and IGF-1 serum levels also increased significantly in the group receiving TPN. Serum cortisol levels increased postoperatively in both groups, which may explain why no significant reduction in serum leptin was observed in the group receiving saline. Free tri-iodothyronine (T3) decreased in both groups, while catecholamines were similar in the groups. CONCLUSION: During fasting and surgical stress, nutrients rapidly increased the serum leptin levels in humans in a manner similar to that previously reported in rodents. This may be mediated by increases in serum glucose, insulin and cortisol.

Adult↗
PubMed2000

In vivo protein synthesis of circulating human T lymphocytes does not respond to a cortisol challenge within 24 h.

BACKGROUND: Although immunocompetence is often measured by assessing responsiveness of lymphocytes to mitogenic stimulation in vitro, this approach may not reflect the in vivo situation. The aim of this investigation was to determine in vivo the protein synthesis rate (FSR) in isolated T lymphocytes and to study the effect of a short-term cortisol infusion on FSR. METHODS: Healthy volunteers (n=24) were randomised into 4 groups. A continuous cortisol infusion (6 microg kg(-1) min(-1)) during 6 h was given to groups 1 and 2, whereas groups 3 and 4 served as control groups and received saline infusion. Protein synthesis was studied before and after 6 h of the cortisol/saline infusion (groups 1 and 3) or 24 h after the start of the infusion (groups 2 and 4). FSR was determined in vivo by the flooding method. The isotopic enrichment of phenylalanine in plasma and lymphocyte protein was determined with gas chromatography-mass spectrometry. RESULTS: The FSR in T lymphocytes was 13.6+/-0.9%/24 h as a mean value (+/-SD) of the first determination in 4 groups. There was no significant difference in FSR from the baseline value immediately after the cortisol infusion (group 1: 13.3+/-1.4%/24 h vs 13.5+/-2.8%/24 h) or 24 h after the start of the infusion (group 2: 13.6+/-0.7%/24 h vs 12.3+/-2.4%/24 h). CONCLUSION: The metabolic activity of circulating T lymphocytes, as reflected by a quantitative measurement of in vivo protein synthesis of human T lymphocytes, was not affected by the increased level of cortisol.

Adult↗
PubMed2000

Methods, who cares?

Explore the source record for details and available documents.

Isotope Labeling↗
PubMed2000

Insulin(GIK) improves myocardial metabolism in patients during blood cardioplegia.

The aim of this study was to test the hypothesis that abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion are attenuated further by insulin(GIK) than by alpha-ketoglutarate enrichment of blood cardioplegia alone. Twenty-eight males (47 to 78 years) undergoing coronary artery bypass grafting (CABG) participated in a prospective, controlled, randomized study. All patients had alpha-ketoglutarate-enriched blood cardioplegia. Insulin(GIK) was infused in 13 patients during aortic cross-clamping. Insulin(GIK) prevented lactate release during cardioplegia (1.5+/-15 vs -44+/-14 micromol/min, p = 0.04), and a significant extraction of lactate was induced shortly after declamping the aorta (15+/-3 vs 2+/-1%, p = 0.001). Free fatty acid uptake was reduced after cardioplegic cross-clamping (5.7+/-1.6 vs 16.0+/-3.8 micromol/min, p = 0.02). More positive/less negative levels of alanine, aspartate, glutamine, glycine, ornithine, taurine and tyrosine were found in all the insulin-treated patients. We conclude that insulin(GIK) attenuates abnormalities of myocardial substrate metabolism during blood cardioplegic aortic cross-clamping and early reperfusion further than is obtained with alpha-ketoglutarate enrichment of blood cardioplegia alone.

Aged↗
PubMed2000

Protein-sparing effect in skeletal muscle of growth hormone treatment in critically ill patients.

OBJECTIVE: To investigate the effect of growth hormone (GH) treatment on skeletal muscle protein catabolism in patients with multiple organ failure in the intensive care unit (ICU). SUMMARY BACKGROUND DATA: Skeletal muscle depletion affects the incidence of complications and the length of hospital stay. A protein-sparing effect of GH treatment in skeletal muscle of long-term ICU patients was hypothesized. METHODS: Twenty critically ill ICU patients were randomized to treatment with GH (0.3 U/kg/day) or as controls. Percutaneous muscle biopsy samples were taken before and after a 5-day treatment period starting on day 3 to 42 of the patient's ICU stay. Protein content, protein synthesis, water, nucleic acids, and free amino acids in muscle were analyzed. RESULTS: The protein content decreased by 8% +/- 11% in the control patients, with no significant change in the GH group. The fractional synthesis rate of muscle proteins increased in the GH group by 33% +/- 48%, and muscle free glutamine increased by 207% +/- 327% in the GH group. Total intramuscular water increased by 12% +/- 14% in the control group as a result of an increase in extracellular water of 67% +/- 86%; these increases were not seen in the GH group. In contrast, the intracellular water increased by 6% +/- 8% in the GH group. CONCLUSION: Treatment with GH for 5 days in patients with multiple organ failure stimulated muscle protein synthesis, increased muscle free glutamine, and increased intracellular muscle water.

APACHE↗
PubMed2000

Effect of hemodialysis on protein synthesis.

BACKGROUND: Earlier studies have shown that hemodialysis (HD) treatment stimulates net protein catabolism. Several factors associated with HD affect protein catabolism, such as an inflammatory effect due to blood-membrane contact and loss of amino acids and glucose into the dialysate. SUBJECTS, MATERIAL AND METHODS: We have studied protein synthesis in skeletal muscle of healthy volunteers (n = 9) before and after a single heparin-free HD. Protein synthesis (PS) was studied, using 2 independent techniques: the incorporation of labeled 2H5-phenylalanine into muscle protein, which gives a quantitative measure of the fractional synthesis rate of muscle proteins, and the concentration and size distribution of ribosomes, which gives a qualitative estimate of protein synthesis. Furthermore, free amino acid concentrations were determined in muscle and plasma. RESULTS: The rate of PS, expressed as the fractional synthesis rate, decreased by 13% during HD (p < 0.02). The capacity for PS, as reflected by the total concentration of ribosomes, was reduced by 22% (p < 0.02) and the activity of PS, expressed as the relative proportion of polyribosomes, decreased from 48.4 +/- 0.9% to 44.8 +/- 0.8% after dialysis (p < 0.01). There was a total loss of 5.8 +/- 0.3 g amino acid to the dialysate. Plasma and muscle free amino acid concentrations were determined at four time points; before and after the phenylalanine incorporation period, before dialysis and before and after the second incorporation period after dialysis. Immediately after dialysis, there was a decrease in plasma asparagine, histidine, alanine, taurine, valine and tryptophane. In muscle, no changes occurred except for a slight increase in leucine after dialysis. In blood, the glucose concentration decreased and the total amount of glucose lost to the dialysate was 21 +/- 3.0 g. In summary, one single hemodialysis treatment decreases fractional protein synthesis rate in skeletal muscle. CONCLUSION: The results demonstrate substantial losses of amino acids and glucose to the dialysate and decreased amino acid concentrations in plasma, but only minimal changes in the intracellular amino acid concentrations in muscle, suggesting that the decreased PS is caused not by lack of amino acid precursors at the site of the synthesis activity, but by other mechanisms.

Adult↗
PubMed1999

Glutamine: a necessary nutrient for the intensive care patient.

Glutamine is a dispensable amino acid, a fact which is particularly important for intensive care patients, and it can be used as an oxidative substrate in processes which require prompt regulation of quantitatively large flows. The production and transport of glutamine from skeletal muscle may be inadequate in patients under intensive care, hence supplemented nutrition has been suggested. Improved long-term survival has been reported, which makes glutamine treatment one of the very few therapeutic strategies that improves outcome in intensive care. This overview deals with the metabolic and physiologic features and updates the clinical documentation of the field.

Glutamine↗
PubMed1999

Glutathione status in critically-ill patients: possibility of modulation by antioxidants.

Muscle tissue serves as a protein reservoir which is mobilized to meet the specific metabolic needs associated with various catabolic conditions in human subjects, such as trauma and critical illness. Glutathione is one of the most abundant short-chain peptides and a major source of non-protein thiol in the body, and tissue glutathione concentration is related to its oxidative capacity. Skeletal muscle is relatively unique with respect to a variety of metabolic properties, such as oxidative potential, patterns of amino acid utilization, and antioxidant enzyme activity. The glutathione concentration is not influenced by food intake, or by food deprivation. Moreover, there is no diurnal variation on muscle glutathione levels. Following elective surgery the muscle concentration of GSH (the reduced form) decreases by 40% 24 h post-operatively, while the concentration of GSSG (the oxidized form) remains unaltered. During critical illness a similar decrease in the GSH concentration is seen, but in addition a change in the redox status indicative of an elevated GSSG level occurs. Furthermore, correlations between the concentrations of glutamine as well as glutamate and GSH exist in these patients. From available evidence accumulated it is clear that glutathione plays a pivotal role in the maintenance of the intracellular redox status, the antioxidant vitamin levels, and the antioxidant enzyme functions under various metabolic conditions. The effectiveness of glutathione protection in the individual tissue depends on the tissue concentration of glutathione as well as the capacity of the tissue to import GSH and to export GSSG. The mechanisms by which catabolism regulates tissue glutathione levels and the enzyme activities associated with the gamma-glutamyl cycle are not completely understood and further studies need to be conducted.

Antioxidants↗